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目的:建立高效液相色谱-紫外(HPLC-UV)方法测定家兔血浆中美托洛尔浓度并进行酒石酸美托洛尔片剂家兔体内药动学研究。方法:以Phenomenex C18柱(250 mm×4.6 mm,5μm)为分析柱,甲醇-水相(60∶40)为流动相(其中水相由385mL水、1.6 mL三乙胺和0.5 mL磷酸组成),紫外检测波长为223 nm,以苯妥英钠为内标,建立HPLC-UV法检测家兔血浆内美托洛尔的浓度。采用DAS3.0.1药动学软件计算药动学参数。结果:美托洛尔的线性范围为0.078～7.81μg·mL-1,最低定量限为0.078μg·mL-1,日内和日间精密度均小于10%,低、中、高3个质控浓度的提取回收率为87.5%～92.3%,准确度的范围在95.4%～108.6%。家兔口服酒石酸美托洛尔片后的主要药动学参数AUC0-t、tmax和Cmax分别为(338.8±30.9)mg.L-1.min、(45.0±0.0)min、(2.2±0.3)μg·mL-1。结论:该方法准确、快速、方便,为美托洛尔的药动学研究提供了简单易行的分析方法。
OBJECTIVE: To establish a high performance liquid chromatography-ultraviolet (HPLC-UV) method for the determination of metoprolol in rabbits plasma and to study the pharmacokinetics of metoprolol tartrate tablets in rabbits. Methods: A Phenomenex C18 column (250 mm × 4.6 mm, 5 μm) was used as the analytical column. The methanol-water phase (60:40) was used as the mobile phase (the aqueous phase consisted of 385 mL of water, 1.6 mL of triethylamine and 0.5 mL of phosphoric acid) , UV detection wavelength of 223 nm, with phenytoin sodium as internal standard, HPLC-UV method was established to detect the concentration of metoprolol in rabbits plasma. Pharmacokinetic parameters were calculated using DAS 3.0.1 pharmacokinetic software. Results: The linear range of metoprolol was 0.078 ~ 7.81μg · mL-1, the lowest limit of quantification was 0.078μg · mL-1, the intra-day and inter-day precision was less than 10%, and the low, middle and high quality control The recovery of the concentration of 87.5% ~ 92.3%, the accuracy of the range of 95.4% ~ 108.6%. The main pharmacokinetic parameters AUC0-t, tmax and Cmax were (338.8 ± 30.9) mg.L-1.min, (45.0 ± 0.0) min, (2.2 ± 0.3) min after oral administration of metoprolol tartrate tablets in rabbits, μg · mL-1. Conclusion: The method is accurate, rapid and convenient for the analysis of metoprolol pharmacokinetics provides a simple and easy method of analysis.